The enzyme-mimicking activity of iron oxide based nanostructures has provided a significant advantage in developing advanced molecular sensors for biomedical and environmental applications. Herein, we introduce the horseradish peroxidase (HRP)-like activity of gold-loaded nanoporous ferric oxide nanocubes (Au-NPFeONC) for the development of a molecular sensor with enhanced electrocatalytic and colorimetric (naked eye) detection of autoantibodies. The results showed that Au-NPFeONC exhibits enhanced peroxidase-like activity toward the catalytic oxidation of 3,3',5,5'-tertamethylbenzidine (TMB) in the presence of HO at room temperature (25 °C) and follows the typical Michaelis-Menten kinetics. The autoantibody sensor based on this intrinsic property of Au-NPFeONC resulted in excellent detection sensitivity [limit of detection (LOD) = 0.08 U/mL] and reproducibility [percent relative standard deviation (% RSD) = <5% for n = 3] for analyzing p53-specific autoantibodies using electrochemical and colorimetric (naked eye) readouts. The clinical applicability of the sensor has been tested in detecting p53-specific autoantibody in plasma obtained from patients with epithelial ovarian cancer high-grade serous subtype (EOCHGS, number of samples = 2) and controls (benign, number of samples = 2). As Au-NPFeONC possess high peroxidase-like activity for the oxidation of TMB in the presence of HO [TMB is a common chromogenic substrate for HRP in enzyme-linked immunosorbent assays (ELISAs)], we envisage that our assay could find a wide range of application in developing ELISA-based sensing approaches in the fields of medicine (i.e., detection of other biomarkers the same as p53 autoantibody), biotechnology, and environmental sciences.
Defects in cilia centrosomal genes cause pleiotropic clinical phenotypes, collectively called ciliopathies. Cilia biogenesis is initiated by the interaction of positive and negative regulators. Centriolar coiled coil protein 110 (CP110) caps the distal end of the mother centriole and is known to act as a suppressor to control the timing of ciliogenesis. Here, we demonstrate that CP110 promotes cilia formation in vivo, in contrast to findings in cultured cells. Cp110−/− mice die shortly after birth owing to organogenesis defects as in ciliopathies. Shh signaling is impaired in null embryos and primary cilia are reduced in multiple tissues. We show that CP110 is required for anchoring of basal bodies to the membrane during cilia formation. CP110 loss resulted in an abnormal distribution of core components of subdistal appendages (SDAs) and of recycling endosomes, which may be associated with premature extension of axonemal microtubules. Our data implicate CP110 in SDA assembly and ciliary vesicle docking, two requisite early steps in cilia formation. We suggest that CP110 has unique context-dependent functions, acting as both a suppressor and a promoter of ciliogenesis.
Exosomes are cell‐derived vesicles secreted by both normal and cancerous cells into the extracellular matrix and in blood circulation. Tumor‐derived exosomes have attracted increasing attention in noninvasive cancer diagnosis and prognosis. However, their effective capture and specific detection pose significant technical challenges. Current detection methods largely fail to quantify the tumor‐derived exosomes present in the total (bulk) exosome population derived from body fluids of cancer patients. In this proof‐of‐concept study, we report an electrochemical detection method to directly quantify the disease‐specific exosomes present in cell culture media. The assay has a two‐step design, where bulk exosome populations are initially captured by using a generic antibody (i.e. tetraspanin biomarker, CD9). Subsequent detection of the cancer‐specific exosomes within the captured exosomes was carried out by using a cancer‐specific antibody, in this case, a human epidermal growth factor receptor 2 (HER‐2) antibody, allowing quantification of HER2‐postive, breast‐cancer‐derived exosomes. This approach exhibits excellent specificity for HER‐2(+) BT‐474 cell‐derived exosomes (detection limit, 4.7×105 exosomes μL−1) with a relative standard deviation of <4.9 % (n=3). We suggest that this simple and inexpensive electrochemical method could be an alternative for the quantification of exosome subpopulations in specific disease settings for future clinical bioassays.
Dermal interstitial fluid (ISF) is a novel source of biomarkers that can be considered as an alternative to blood sampling for disease diagnosis and treatment. Nevertheless, in vivo extraction and analysis of ISF are challenging. On the other hand, microneedle (MN) technology can address most of the challenges associated with dermal ISF extraction and is well suited for long-term, continuous ISF monitoring as well as in situ detection. In this review, we first briefly summarise the different dermal ISF collection methods and compare them with MN methods. Next, we elaborate on the design considerations and biocompatibility of MNs. Subsequently, the fabrication technologies of various MNs used for dermal ISF extraction, including solid MNs, hollow MNs, porous MNs, and hydrogel MNs, are thoroughly explained. In addition, different sensing mechanisms of ISF detection are discussed in detail. Subsequently, we identify the challenges and propose the possible solutions associated with ISF extraction. A detailed investigation is provided for the transport and sampling mechanism of ISF in vivo. Also, the current in vitro skin model integrated with the MN arrays is discussed. Finally, future directions to develop a point-of-care (POC) device to sample ISF are proposed.
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